Multiple roles for NaV1.9 in the activation of visceral afferents by noxious inflammatory, mechanical, and human disease–derived stimuli

Abstract

SummaryNaV1.9 regulates normal colonic afferent mechanosensation and is required for hypersensitivity to noxious inflammatory mediators and those derived from inflammatory bowel disease tissues.

The Domain II S4-S5 Linker in Nav1.9: A Missense Mutation Enhances Activation, Impairs Fast Inactivation, and Produces Human Painful Neuropathy

“…d Responses of a small DRG neuron transfected with G699R mutant channels to the subthreshold (130-135 pA) and the threshold depolarizing current injections (140 pA). Arrows with numbers indicate the current amplitude used to elicit the labeled response Neuromol Med Amaya et al 2006;Ostman et al 2008;Lolignier et al 2011) and have implicated Nav1.9 in bone cancer pain (Qiu et al 2012) and visceral pain (Hockley et al 2014).…”

NaV1.9: a sodium channel linked to human pain

“…This preferential cellular distribution of Na V 1.9 may contribute to the distinct firing properties of IB4 + neurons 15 . However, it has recently been shown that Na V 1.9 is predominantly present in IB4 − peptidergic DRG neurons that innervate the colon 20 . Irrespective of the cell type in which it is expressed, the presence of Na V 1.9 in the peripheral and central termini of primary afferents suggests that the channel has a role in the integration of receptor potentials and possibly in Na V 1.9: a sodium channel linked to human pain Sulayman D. Dib-Hajj, Joel A.…”

Modulation of intracranial meningeal nociceptor activity by cortical spreading depression: a reassessment

“…It is noteworthy that this sensitivity is unlikely to be related to the propensity of the neurons to become activated in response to a chemical stimulus evoked by ATP or the mixture of inflammatory mediators tested given that we did not find any difference in the responsiveness to these nociceptive agents between neurons that were affected by CSD and those that did not. Finally, the short duration of the nociceptors' activation after stimulation with ATP, similar to its action on nociceptors innervating other tissues (Hockley et al 2014;Jankowski et al 2013), suggest that local action of ATP may not play a significant role, at least not by itself, in mediating the prolonged nociceptor response after CSD.…”

“…For ATP stimulation, we applied freshly made ATP (1 mM in pH 7.2 SIF). Chemical stimuli were applied for 180 s and the concentrations used were based on previous finding (Hockley et al 2014;Jankowski et al 2013;Levy and Strassman 2002a). Units were stimulated with IM, ATP, or both agents.…”

“…For calculating the onset latency for such activation, time 0 was considered as the time when the first sign of the CSD (i.e., the initial increase in cerebral blood flow) appeared. Activation by IM or ATP was considered when the discharge rate increased above the upper end point of the 95% confidence interval for the baseline mean for duration of at least 60 s for ATP and 300 s for IM (Hockley et al 2014;Jankowski et al 2013;Levy and Strassman 2002a). Group differences were analyzed using two-tailed, Fisher's exact test.…”